eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
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6/2020
vol. 16
 
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Lipid disorders
abstract:
Research letter

Statins and C-reactive protein: in silico evidence on direct interaction

Neda Shakour
1
,
Massimiliano Ruscica
2
,
Farzin Hadizadeh
3
,
Cesare Cirtori
4
,
Maciej Banach
5, 6
,
Tannaz Jamialahmadi
7, 8
,
Amirhossein Sahebkar
3, 9, 10

1.
Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
2.
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy
3.
Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
4.
Centro Dislipidemie, A.S.S.T. Grande Ospedale Metropolitano Niguarda, Milan, Italy
5.
Department of Hypertension, WAM University Hospital, Medical University of Lodz, Lodz, Poland
6.
Polish Mother’s Memorial Hospital Research Institute (PMMHRI), Lodz, Poland
7.
Department of Food Science and Technology, Quchan Branch, Islamic Azad University, Quchan, Iran
8.
Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
9.
Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
10.
Halal Research Center of IRI, FDA, Tehran, Iran
Arch Med Sci 2020; 16 (6): 1432–1439
Online publish date: 2020/11/02
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Introduction
Statins are known to lower CRP, and this reduction has been suggested to contribute to the established efficacy of these drugs in reducing cardiovascular events and outcomes. However, the exact mechanism underlying the CRP-lowering effect of statins remains elusive.

Material and methods
In order to test the possibility of direct interaction, we performed an in silico study by testing the orientation of the respective ligands (statins) and phosphorylcholine (the standard ligand of CRP) in the CRP active site using Molecular Operating Environment (MOE) software.

Results
Docking experiments showed that all statins could directly interact with CRP. Among statins, rosuvastatin had the strongest interaction with CRP (pKi = 16.14), followed by fluvastatin (pKi = 15.58), pitavastatin (pKi = 15.26), atorvastatin (pKi = 14.68), pravastatin (pKi = 13.95), simvastatin (pKi = 7.98) and lovastatin (pKi = 7.10). According to the above-mentioned results, rosuvastatin, fluvastatin, pitavastatin and atorvastatin were found to have stronger binding to CRP compared with the standard ligand phosphocholine (pKi = 14.55).

Conclusions
This finding suggests a new mechanism of interaction between statins and CRP that could be independent of the putative cholesterol-lowering activity of statins.

keywords:

C-reactive protein, statins, inflammation, docking, interaction

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